Lactoperoxidase, hydrogen peroxide and thiocyanate ion form a bacteriostatic system in saliva. The peroxidase-catalyzed oxidation of thiocyanate yeilds hypothiocyanite anion. This antibacterial agent oxidizes a portion of the sulfhydryl components of bacteria, causing inhibition of essential functions and inhibition of growth. However, bacteria can recover from this limited oxidation of sylfhydryls. The inhibition of bacterial functions by the peroxidase system and the mechanism of recovery will be investigated, using the cariogenic organism, Streptococcus mutans. It will be determined whether the peroxidase system inhibits functions that may contribute to the cariogenic activity of S. mutans, including extracellular dextran synthesis, dextran-induced aggregation and lactic acid excretion. Also these studies will identify the bacterial functions that are not inhibited and which contribute to the recovery process. The experiments will be carried out using purified components and in saliva, so as to determine whether other components of saliva modify peroxidase action, and whether components of saliva are chemically modified by hypothiocyanite. These studies should help to assess the importance of the peroxidase system in saliva, and establish a rational basis for increasing the antibacterial action by blocking recovery. The location of oxidized sulfhydryls within the bacteria will be determined to evaluate the hypothesis that the limited oxidation of bacterial components is due to the inability of hypothiocyanite ion to penetrate the bacterial cell envelope. Two approaches will be taken to increasing the access of hypothiocyanite to intracellular components: 1. increasing the permeability of the cell envelope, and 2. chemically modifying the hypothiocyanite ion to produce a membrane-soluble oxidizing agent. The objectives are to increase the efficacy or selectivity of peroxidase antibacterial action in ways that will be relevant to the oral environment. In addition, these studies will determine which of the chemical assays for peroxidase action may have value as clinical tests for antimicrobial activity and microbial susceptibility in saliva.